The enclosed proposal is requesting funds to expand the mass spectrometry and proteomics resources at the University of Washington through the purchase of a Thermo Fisher LTQ-Orbitrap mass spectrometer. This instrument will be invaluable in the successful completion of our existing NIH funded projects involving the qualitative and quantitative analysis of proteins and protein modifications of complex mixtures. Furthermore, a number of our projects are extending quantitative proteomics technology to the measurement of changes in the rate of turnover. Integral to the timely completion of these NIH research projects is the availability of a mass spectrometer capable of i) sub 5 ppm mass accuracy to distinguish between similar mass peptides, ii) a dynamic range of >1000 in a single spectrum, iii) data-dependent acquisition of tandem mass spectra with the sensitivity and speed of a quadrupole ion trap, and iv) the ability to resolve and detect unusual isotope distributions of multiply charged peptides within a complex mixture. Current mass spectrometers capable of these measurements are oversubscribed and, thus, can provide little to no access to our grants user groups. We propose to address these limitations through the acquisition of a shared hybrid mass spectrometer which combines the robustness and speed of a linear quadrupole ion-trap with the resolution, mass accuracy, and dynamic range of a Fourier transform mass spectrometer. The requested instrumentation will allow the faculty to address current technological limitations on a global level and improve the sample analysis bottleneck that will improve the capabilities of existing and future NIH funded projects within the University of Washington, College of Medicine. PUBLIC HEALTH RELEVANCE: We are requesting support to purchase a mass spectrometer for the qualitative and quantitative analysis of complex protein mixtures. These analyses will be used to improve our understanding of how a genome sequence encodes a functional living organism, to identify novel reproductive proteins, identify biomarkers of exposure to environmental toxins, understanding the molecular machinery responsible for double stranded DNA breaks, the basic molecular processes involved in aging, and more. All of these areas improve our understanding, prevention, or treatment of human disease.